Innova Vascular OVER-THE-WIRE

Transcription

1 POTENTIAL ADVERSE EVENTS... HOW SUPPLIED Innova Vascular OVER-THE-WIRE Self-Expanding Stent System TABLE OF CONTENTS < en > WARNING... DEVICE DESCRIPTION... Contents... INTENDED USE / INDICATIONS FOR USE... CONTRAINDICATIONS... WARNINGS... PRECAUTIONS... MAGNETIC RESONANCE IMAGING (MRI) SAFETY INFORMATION... RF Heating... Image Artifact... CLINICAL STUDIES... The SuperNOVA Study... Table : Baseline Demographics and Clinical Characteristics Overall (N=99)...3 Table : Baseline Site-Reported Lesion Characteristics (N=99 Lesions)...3 Table 3: Angiographic Core Lab Baseline Measurements (N=99 Lesions)...4 Table 4: Primary Safety Endpoint and Components (N=99 Subjects)...4 Table 5: Secondary Safety Endpoint and Components (N=99 Subjects)...4 Table 6: Serious Adverse Events by MedDRA System/Organ Class...5 Table 7: Co-Primary Effectiveness Endpoints (N=99)...5 Figure. Primary Patency in Core Stents through Months...5 Table 8: Primary Patency in Core Stents Subjects through Months...5 Figure. Primary Patency in All Stents through Months...5 Table 9: Primary Patency in All Stents through Months...5 Table 0: Technical and Procedural Success (N=99)...6 Table : Analysis of Secondary Effectiveness Endpoints (N= 99)...6 Handling and Storage...6 RECOMMENDED MATERIALS...6 OPERATIONAL INSTRUCTIONS...6 Patient Preparation...6 Inject Contrast Media...6 Evaluate and Mark the Stenosis...6 Select Proper Stent System...6 Table. Innova Vascular Self-Expanding Stent System Models and Sizes...6 Preparation of Stent Delivery System...7 Figure Delivery Procedures...7 Stent Deployment Procedure (Reference Figure 3)...7 Figure Recommended Method of Deployment...7 Figure Post Procedure...8 REFERENCES...8 WARRANTY...8 ONLY Caution: Federal Law (USA) restricts this device to sale by or on the order of a physician. WARNING Contents supplied STERILE using an ethylene oxide (EO) process. Do not use if sterile barrier is damaged. If damage is found, call your Boston Scientific representative. For single use only. Do not reuse, reprocess or resterilize. Reuse, reprocessing, or resterilization may compromise the structural integrity of the device and/or lead to device failure which, in turn, may result in patient injury, illness or death. Reuse, reprocessing or resterilization may also create a risk of contamination of the device and/or cause patient infection or cross-infection, including, but not limited to, the transmission of infectious disease(s) from one patient to another. Contamination of the device may lead to injury, illness or death of the patient. After use, dispose of product and packaging in accordance with hospital, administrative and/or local government policy. Carefully read all instructions prior to use. Observe all warnings and precautions noted throughout these instructions. Failure to do so may result in complications. DEVICE DESCRIPTION The Innova Vascular Self-Expanding Stent System is comprised of two components: the implantable endoprosthesis and the stent delivery system. The stent is a laser cut self-expanding stent composed of a nickel titanium alloy (Nitinol). On both the proximal and distal ends of the stent, radiopaque markers made of tantalum increase visibility of the stent to aid in placement. The stent is constrained within a 6F (. mm maximum OD) delivery system. The delivery system is a triaxial design with an outer shaft to stabilize the stent delivery system, a middle shaft to protect and constrain the stent, and an inner shaft to provide a guidewire lumen. The delivery system is compatible with in (0.89 mm) guidewires. See Figure 3 for a device diagram and Table for a device size matrix. Prior to use, please refer to the OPERATIONAL INSTRUCTIONS. Contents One () Innova Vascular Self-Expanding Stent System INTENDED USE / INDICATIONS FOR USE The Innova Vascular Self-Expanding Stent System is indicated to improve luminal diameter in the treatment of symptomatic de-novo or restenotic lesions in the native superficial femoral artery (SFA) and/or proximal popliteal artery (PPA) with reference vessel diameters from 4.0 mm to 7.0 mm and lesion lengths up to 90 mm. CONTRAINDICATIONS Patients with contraindication to antiplatelet and/or anticoagulation therapy. Patients who are judged to have a lesion that prevents proper placement or deployment of the stent. A lesion that is within an aneurysm or an aneurysm with a proximal or distal segment to the lesion. Patients who exhibit angiographic evidence of severe thrombus in the target vessel or lesion site before/after undergoing Percutaneous Transluminal Angioplasty (PTA) procedure. A lesion through which a guide wire cannot pass. WARNINGS Do not use after the Use By date specified on the package. Ensure that the device has been properly stored in a cool, dark, dry place not to exceed 5 C (4 F). Do not use if the temperature exposure indicator dot on the pouch label is red or missing. Do not expose to organic solvents (e.g. alcohol). Stenting across a bifurcation or side branch could compromise future diagnostic or therapeutic procedures. The stent is not designed for repositioning; once the stent is partially deployed, it cannot be recaptured or reconstrained using the stent delivery system. PRECAUTIONS The delivery system is not designed for use with power injection systems. Do not use a kinked delivery system. Only advance the stent delivery system over a stiff in guidewire. Always use an introducer or guide sheath for the implant procedure, to protect the access site. If strong resistance is met with the introduction of the delivery system or if unable to initiate release of the stent, remove the entire system from the patient and introduce a new system. Never post-dilate the stent using a balloon that is larger in diameter than the nominal (labeled) diameter of the stent. When catheters are in the body, they should be manipulated only under fluoroscopy. Radiographic equipment that provides high quality images is needed. The stent delivery system is not intended for arterial blood monitoring. The minimally acceptable introducer or guide sheath size is printed on the package label. Do not attempt to pass the stent delivery system through a smaller size introducer or guide sheath than indicated on the label. Do not remove the thumbwheel lock prior to deployment. Premature removal of the thumbwheel lock may result in an unintended deployment of the stent. Boston Scientific (Master Brand DFU Template 8.677in x.699in A4, 9000AA), edfu, MB, Innova Vascular, en, B CV0

2 Prior to deployment, ensure adequate distance between the proximal end of stent and the introducer/guide sheath to prevent deployment within introducer/guide sheath. This device has not been tested in patients who are pregnant or patients who may be pregnant. Take caution when considering whether to use this device in patients with known allergy to nickel-titanium alloy or contrast media. Take caution when considering whether to use this device in vessel in which there may be a residual stenosis of 50% diameter or larger in the target vessel after the planned intervention. In patients with poor kidney function, contrast agents may precipitate kidney failure. MAGNETIC RESONANCE IMAGING (MRI) SAFETY INFORMATION MR Magnetic Resonance Conditional A patient with this device can be scanned safely only under specific conditions. Failure to follow the conditions may result in severe injury. Non-clinical testing has demonstrated the Innova Stents are MR Conditional for single and overlapping lengths up to 00 mm. A patient with this stent can be scanned safely, immediately after placement, under the following conditions: Static magnetic field of.5 or 3.0 Tesla Highest spatial gradient magnetic field of 40 Tesla/m (4,000 Gauss/cm) or less Maximum MR system reported whole body averaged specific absorption rate (SAR) of W/kg for landmarks (i.e. center of RF coil) above the umbilicus W/kg for landmarks below the umbilicus RF Heating Under the scan conditions defined above, the Innova Stent is expected to produce a maximum in-vivo temperature rise of 4.3 C after 5 minutes of continuous scanning. Image Artifact In non-clinical testing, the image artifact caused by the device extends approximately mm from the Innova stent when imaged with a gradient echo pulse sequence and a 3 Tesla MRI system. The artifact does obscure the device lumen. POTENTIAL ADVERSE EVENTS Based on the literature and on clinical and commercial experience with self-expanding stents, the following list includes some possible adverse events associated with the use of the device or the stenting procedure. Allergic reaction (to drug, contrast, device or other) Angina Aneurysm Arrhythmia Arteriovenous fistula Bleeding/Hemorrhage Bradycardia Death Drug reactions Embolization (air, plaque, thrombus, device, tissue, or other) Extremity ischemia/amputation Fever Hematoma Leg pain/claudication Myocardial Infarction Nausea or vomiting Need for urgent intervention or surgery Pseudoaneurysm formation Renal insufficiency or failure Restenosis of stented artery Sepsis/infection Stent fracture Stent migration Stent misplacement/jumping Stroke Target Lesion Revascularization Thrombosis/thrombus Tissue ischemia/necrosis Transient hemodynamic instability (hypotensive/hypertensive episodes) Vasospasm Vessel injury, including perforation, trauma, rupture and dissection Vessel occlusion CLINICAL STUDIES The clinical evidence supporting the safety and effectiveness of the Innova Self-Expanding Stent System for the treatment of symptomatic de-novo or restenotic lesions in the native superficial femoral artery (SFA) and/or proximal popliteal artery (PPA) with reference vessel diameters from 4.0 to 7.0 mm is from the SuperNOVA study. The SuperNOVA Study A study titled SuperNOVA: Stenting of the Superficial Femoral and Proximal Popliteal Arteries with the Boston Scientific Innova Self-Expanding Bare Metal Stent System (SuperNOVA) was conducted. The SuperNOVA study is a prospective, single arm, controlled, multicenter, global clinical trial designed to treat stenosed superficial femoral and proximal popliteal arteries by implanting the Innova Self-Expanding Stent. Its objective was to prospectively evaluate the safety and effectiveness of the Innova Self-Expanding Stent System in SFA/PPA by comparing to Performance Goals of PTA alone in the treatment of atherosclerotic lesions of the native superficial femoral artery (SFA) or the superficial femoral and proximal popliteal arteries. The performance goals were based on an aggregate of published trial data as described by VIVA Physicians Inc. (VPI). A total of 99 subjects requiring treatment of symptomatic de-novo or restenotic lesions in the native SFA and/or PPA with reference vessel diameters ranging from 4.0 mm -7.0 mm were enrolled and treated with the Innova Self-Expanding Stent System. Thirty-nine (39) of the stented segments were treated with the long stents (80 mm or 00 mm). The remaining 60 stented segments were treated with the core stent matrix (0 mm to 50 mm). Subjects were enrolled by 49 centers located in the United States, Europe, Canada and Japan. The follow-up period after the index procedure is ongoing and set for 3 years (or 5 years in Japan only) in subjects successfully implanted with the Innova stent(s). Eligible subjects were 8 years or older who consented to participate. These subjects had documented peripheral artery disease defined as Rutherford categories, 3, or 4 and evidence of a stenotic, restenotic (from angioplasty only) or occlusive lesion(s) located in the native superficial femoral artery or proximal popliteal artery with degree of stenosis 70% by visual angiographic assessment. The vessel diameter was 4 mm and 7 mm and total lesion length was 30 mm and 90 mm located at least 3 cm above the inferior edge of the femur. Subject follow-up occurred at 30 days, 6 months, months, years and 3 years (4 and 5 years for subjects at Japan sites only). The first subject was enrolled April, 0. Enrollment completed June 8, 03. The database for this study reflects data collected through August 4, 04. The primary study endpoints were as follows: The primary safety endpoint was a composite of Major Adverse Events (MAE) defined as all causes of death through month post-index procedure, target limb major amputation through months post-index procedure and/or Target Lesion Revascularization (TLR) through months post-index procedure. The primary safety endpoint assessed the composite MAE rate in order to demonstrate a month MAE-free rate exceeds the performance goal (PG) of 59.6%. The co-primary effectiveness endpoints assessed primary stent patency rate at months. Primary patency was defined as the percentage of lesions (target stented segments) that reach endpoint without a hemodynamically significant stenosis on DUS (Systolic Velocity (PSV) ratio <.4), and without TLR or bypass of the target lesion. The co-primary effectiveness endpoint () assessed stented segments intended to be treated with the core stent matrix (stent lengths from 0 mm to 50 mm) in order to demonstrate that the month vessel primary patency rate exceeds the PG of 66%. The co-primary effectiveness endpoint () assessed stented segments intended to be treated with the entire stent matrix (stent lengths from 0 mm to 00 mm) in order to demonstrate that the month vessel primary patency rate exceeds the PG of 63%. In addition to rejecting the null hypothesis, a non-statistically driven goal needed to be observed, such that the rate of vessel primary patency at months observed with the long stents must be 50%. Rocha-Singh KJ, et.al. Performance Goals and Endpoint Assessments for Clinical Trials of Femoropopliteal Bare Nitinol Stents in Patients with Symptomatic Peripheral Arterial Disease. Catheterization and Cardiovascular Interventions 007;69: The SuperNOVA Study employed independent duplex ultrasound, x-ray and angiographic core laboratories to review and analyze key study variables. An independent data reviewer was used to review study data on an ongoing basis and identify any potential safety trends. Adjudication of any potential major adverse events was conducted by an independent Clinical Events Committee (CEC). Boston Scientific (Master Brand DFU Template 8.677in x.699in A4, 9000AA), edfu, MB, Innova Vascular, en, B

3 Patient Population Table provides a review of baseline demographics and clinical characteristics of the 99 subjects enrolled into the SuperNOVA study. Table : Baseline Demographics and Clinical Characteristics Overall (N=99) Age (Year) 67.4±9.7 (99) (45.0, 93.0) Male Gender 74.% (/99) Race/Ethnicity Hispanic or Latino.3% (4/99) Caucasian 79.6% (38/99) Asian 4.0% (4/99) Black, or African heritage 4.3% (3/99) Native Hawaiian or other Pacific Islander 0.3% (/99) American Indian or Alaska Native 0.3% (/99) Other 0.0% (0/99) Not Disclosed 0.0% (0/99) General Medical History History of Smoking 83.9% (5/99) Current Diabetes Mellitus 40.5% (/99) Type.3% (7/99) Type 36.8% (0/99) Unknown.3% (4/99) Medically-Treated Diabetes 35.% (05/99) History of Hyperlipidemia requiring medication 74.9% (4/99) History of Hypertension requiring medication 79.9% (39/99) History of Chronic Obstructive Pulmonary Disease 8.4% (5/99) Cardiac History History of Coronary Artery Disease 43.5% (30/99) History of Myocardial Infarction (MI) 4.7% (74/99) History of Congestive Heart Failure 8.4% (5/99) New York Heart Assoc. (NYHA) Classification I.3% (4/99) II.7% (8/99) III.3% (4/99) IV 0.3% (/99) Unknown.7% (8/99) History of Percutaneous Coronary Intervention (PCI) History of Coronary Artery Bypass Graft (CABG) Surgery Current Angina Status Neurologic/Renal History 8.4% (85/99) 8.% (54/99) Stable Angina 4.7% (44/99) Unstable Angina 0.3% (/99) None 8.9% (45/99) History of Transient Ischemic Attacks (TIA) History of Cerebrovascular Accident (CVA) 7.0% (/99) 8.0% (4/99) History of Renal Insufficiency 0.4% (3/99) History of Renal Percutaneous Intervention Peripheral Vascular History History of Peripheral Vascular Surgery History of Other Peripheral Endovascular Interventions Values include the mean plus/minus standard deviation and range..3% (4/99) 9.0% (7/99) 4.8% (5/99) History of Claudication 94.0% (8/99) 3 Lesion Characteristics Table and Table 3 present the site-reported and angiographic core lab assessed lesion characteristics, respectively. Table : Baseline Site-Reported Lesion Characteristics (N=99 Lesions) Treated Limb Overall Right leg 46.% (38/99) Left leg 53.8% (6/99) Arterial Segments Proximal.0% (33/99) Mid 58.% (74/99) Distal 58.% (74/99) Ostial 0.3% (/99) Proximal Popliteal Artery 5.7% (47/99) Target Lesion Reference Vessel Diameter (RVD, mm) 5.6±0.7 (99) (4.0, 7.0) Target Lesion % Diameter Stenosis 9.7±9. (99) (70.0, 00.0) Target Lesion Length (mm) 90.8±44.4 (99) (30.0, 90.0) Thrombus Seen.3% (7/99) TASC II Lesion Classification Predilation A 40.5% (/99) B 4.% (6/99) C 3.7% (4/99) D 3.7% (/99) Predilation Performed 8.9% (45/99) If Yes, Number of Predilation Balloons Used.±0.4 (45) (.0, 5.0) Post-Deployment Dilation Post-Deployment Dilation Performed 96.7% (89/99) If Yes, Number of Post-deployment Balloons Used.±0.4 (89) (.0, 3.0) Target Lesion Final Outcome Final % Stenosis 4.±8. (99) (0.0, 50.0) Thrombus seen in treated vessel at the end of the procedure Values include the mean plus/minus standard deviation and range. Subjects under Arterial Segments may have checked more than one location present. 0.7% (/99) Boston Scientific (Master Brand DFU Template 8.677in x.699in A4, 9000AA), edfu, MB, Innova Vascular, en, B

4 Table 3: Angiographic Core Lab Baseline Measurements (N=99 Lesions) Treated Limb Right leg 45.6% (36/98) Left leg 54.4% (6/98) Arterial Segments 3 Proximal 0.4% (3/98) Mid 57.0% (70/98) Distal 67.4% (0/98) Ostial.7% (5/98) Proximal Popliteal Artery 5.% (45/98) Distance from Ostium (mm) 00.±54. (75) (0.0, 33.) Length (mm) 93.±49. (93) (0., 84.7) Reference Vessel Diameter (RVD) (mm) 5.0±0.9 (95) (.9,7.6) Lesion Type Eccentric Lesion 46.6% (39/98) Concentric Lesion 5.3% (56/98) Bend (degrees) Thrombus 4 Calcification >45 degrees 0.0% (0/98) >90 degrees 0.0% (0/98) Grade % (9/98) Grade 0.7% (/98) Grade 0.3% (/98) Grade 3 0.3% (/98) Grade 4 0.0% (0/98) Grade 5 0.0% (0/98) None/Mild 9.5% (88/98) Moderate 34.6% (03/98) Severe 35.6% (06/98) Ulceration (Present) 3.4% (40/98) Aneurysm (Present) 3.4% (0/98) Patency to Foot No Infrapopliteal Vessel Patent 9.% (3/50) Infrapopliteal Vessel Patent 30.0% (75/50) Infrapopliteal Vessels Patent 37.6% (94/50) 3 Infrapopliteal Vessels Patent 3.% (58/50) Anterior Tibial Artery Patent 37.6% (/98) Posterior Tibial Artery Patent 54.0% (6/98) Peroneal Artery Patent 56.7% (69/98) Profunda Femoris Artery Patent 66.% (97/98) Values include the mean plus/minus standard deviation and range. Core lab reported Treated Limb may differ from the site reported Treated Limb. 3 Subjects under Arterial Segments may have checked more than one location present 4 Thrombus could have subjects with N/A response as allowed by CRF so percentages may not add up to 00%. 4 Study Results Primary Safety Endpoint Results Table 4 summarizes the primary safety endpoint results for the SuperNOVA study. The month MAE free rate was 85.8% with the lower 95% Confidence Interval (CI) exceeding the established PG of 59.6%. Table 4: Primary Safety Endpoint and Components (N=99 Subjects) Primary Safety Endpoint Overall 95% CI Lower -Sided -Month Freedom from MAE 85.8% (30/68) -Month MAE (Composite Endpoint) 4.% (38/68) All Causes of Deaths at Month 0.0% (0/68) Target Limb Major Amputation 0.4% (/68) Target Lesion Revascularization (TLR) 4.% (38/68) 97.5% CI PG [8.%, 89.8%] 8.% 59.6% (Met) Twelve-Month Major Adverse Events (MAEs) defined as all causes of death through month, target limb major amputation through months and/or target lesion revascularization through months. Binomial Exact Method Abbreviation: PG, Performance Goal Secondary Safety Endpoints Results Table 5 summarizes the secondary safety endpoint results for the SuperNOVA study. The month MAE free rate was 99.7%. Table 5: Secondary Safety Endpoint and Components (N=99 Subjects) Secondary Safety Endpoint Overall 95% CI Lower -Sided 97.5% CI -Month Freedom from MAE 99.7% (96/97) [98.%, 00.0%] 98.% -Month MAE (Composite Endpoint) 0.3% (/97) All Causes of Deaths 0.0% (0/97) Target Limb Major Amputation Target Lesion Revascularization (TLR) 0.0% (0/97) 0.3% (/97) One-month Major Adverse Events (MAEs) defined as all causes of death, target limb major amputation and/or target lesion revascularization through month. Binomial Exact Method Abbreviation: PG, Performance Goal PG 88.0% (Met) Boston Scientific (Master Brand DFU Template 8.677in x.699in A4, 9000AA), edfu, MB, Innova Vascular, en, B

5 Evaluation of Safety Table 6 displays the rates of Serious Adverse Events (SAEs) reported by MedDRA System/Organ Class (SOC). The sub-categories are Preferred Terms (PTs), and include only those SAEs that were reported by the treating physician as related to the device and/or the procdure. As presented in Figure and Table 8, the freedom from loss of primary patency at months for the core stent matrix was 76.7%. Table 6: Serious Adverse Events by MedDRA System/Organ Class Serious Adverse Event by SOC and PT Events Rate of Subjects With Event Any serious adverse event % (47/99) Not coded 4 0.7% (/99) Cardiac disorders % (5/99) Congenital, familial and genetic disorders 0.3% (/99) Gastrointestinal disorders 8 4.3% (3/99) Retroperitoneal hematoma 0.7% (/99) General disorders and administration site conditions 4 4.3% (3/99) Catheter site hemorrhage 0.7% (/99) Impaired healing 0.3% (/99) Immune system disorders 0.7% (/99) Infections and infestations 8 5.7% (7/99) Catheter site infection 0.3% (/99) Localized infection 0.3% (/99) Injury, poisoning and procedural complications 5.7% (7/99) Arterial injury 0.3% (/99) Metabolism and nutrition disorders 3.0% (3/99) Musculoskeletal and connective tissue disorders 4 4.0% (/99) Pain in extremity 0.7% (/99) Neoplasms benign, malignant and unspecified (incl cysts and polyps) 9.7% (8/99) Nervous system disorders 9.3% (7/99) Renal and urinary disorders 5.7% (5/99) Reproductive system and breast disorders 0.3% (/99) Respiratory, thoracic and mediastinal disorders 3.0% (3/99) Skin and subcutaneous tissue disorders 0.7% (/99) Surgical and medical procedures 0.3% (/99) Vascular disorders 48 8.% (84/99) Arterial thrombosis limb 5.3% (4/99) Femoral arterial stenosis % (3/99) Femoral artery dissection 0.3% (/99) Femoral artery occlusion 8.7% (5/99) Intermittent claudication 7.0% (6/99) Peripheral arterial occlusive disease 0.3% (/99) All PTs that were experienced are not listed. The PTs that are listed are physician-reported to be either device and/or procedure-related. Primary Effectiveness Endpoint Results Table 7 presents primary patency results for the co-primary effectiveness endpoints incorporated into the SuperNOVA study. The performance goal of 66% was not met. Table 7: Co-Primary Effectiveness Endpoints (N=99) Overall 95% CI Lower -Sided % CI -Month Primary Patency in Core 69.5% (57/6) [63.0%, 75.4%] 63.0% Matrix Stents -Month Primary Patency in Entire Stent Matrix 66.4% (74/6) -Month Primary Patency in Long Stents 3,4 47.% (7/36) PG 66.0% (Not Met) Core Matrix Stents (0-50 mm) 3 Long Stents (80-00 mm) 5 Binomial Exact Method Entire Stent Matrix (0-00 mm) 4 The observed rate must be 50.0% Abbreviation: PG, Performance Goal 5 Figure. Primary Patency in Core Stents through Months Table 8: Primary Patency in Core Stents Subjects through Months Number of Subjects Time from Index Procedure (months) Entered Censored At Risk Events Events/Month Event Rate 0% 0.4%.0%.0%.0%.8% 6.6% 3.3% Event Free 00% 99.6% 98.0% 98.0% 98.0% 97.% 93.4% 76.7% Std Error 0% 0.4% 0.9% 0.9% 0.9%.0%.6% 3.0% SVS SE 0% 0.4% 0.9% 0.9% 0.9% %.6%.8% At risk=entered-0.5 Censored Subjects event-free at months or later are censored at greater than months. Intervals are end inclusive, e.g. interval 6 is defined as 4-6 months, inclusive. Event rate and standard error estimates are for interval end. Standard errors by Greenwood formula As presented in Figure and Table 9, the freedom from loss of primary patency at months for the entire stent matrix was 73.7%. Figure. Primary Patency in All Stents through Months Table 9: Primary Patency in All Stents through Months Time from Index Procedure (months) Number of Subjects Entered Censored At Risk Events Events/Month Event Rate 0% 0.3%.7%.7%.% 4.% 0.0% 6.3% Event Free 00% 99.7% 98.3% 98.3% 97.9% 95.8% 90.0% 73.7% Std Error 0% 0.3% 0.8% 0.8% 0.8%.%.8%.9% SVS SE 0% 0.3% 0.8% 0.8% 0.8%.%.7%.6% At risk= Entered- 0.5 Censored Subjects event-free at months or later are censored at greater than months. Intervals are end inclusive, e.g. interval 6 is defined as 4-6 months, inclusive. Event rate and standard error estimates are for interval end. Standard errors by Greenwood formula Boston Scientific (Master Brand DFU Template 8.677in x.699in A4, 9000AA), edfu, MB, Innova Vascular, en, B

6 Secondary Effectiveness Endpoint Results The secondary effectiveness endpoints are summarized in Table 0 and Table below. Table 0: Technical and Procedural Success (N=99) Overall Technical Success 99.0% (96/99) Procedure Success 99.0% (96/99) Technical success was defined as the ability to cross and dilate the lesion to achieve residual angiographic stenosis no greater than 30%. Procedural success is defined as technical success with no MAEs within 4 hours of the index procedure. Table : Analysis of Secondary Effectiveness Endpoints (N= 99) Primary Patency at Months 66.4% (74/6) Primary Patency for Core Stent Matrix at Months 69.5% (57/6) Assisted Primary Patency at Months 83.8% (07/47) Assisted Primary Patency for Core Stent Matrix at Months 85.5% (83/4) Target Vessel Revascularization (TVR) Rate at Months 3.8% (38/75) Target Lesion Revascularization (TLR) Rate at Months 3.8% (38/75) Improvement in the Rutherford Clinical Improvement Scale of at months without the need for repeat TLR Improvement in the Rutherford Clinical Improvement Scale of at months including subjects with repeat TLR Increase in ABI of 0.0 or to an ABI 0.90 as compared to pre-procedure without the need for repeat TLR Walking Improvement Change in Walking Impairment Questionnaire Score from Baseline to Months Walking Improvement Change in Total Distance Walked over 6 Minutes from Baseline to Months 79.5% (09/63) 90.% (37/63) 59.0% (64/78) 34.03±37. (63) (-50.00, 00.00) 69.3±30. (35) (-94.0, 033.0) Stent Fracture Rate at Months.9% (6/38) Values include the mean plus/minus standard deviation and range. Subgroup Analyses Gender: The female population had a higher overall TLR rate (.4% vs..4%) and a lower month primary patency rate in the core stents matrix (55.6% vs 73.8%) than the male population. The female subgroup was slightly older with a greater prevalence of Rutherford classification 3 and 4 as well as hypertension compared to the male subgroup. The male subgroup had a higher prevalence of diabetes and coronary artery disease than the female subgroup. Despite these differences and the differences observed for patency in the core stent matrix, both female and male subgroups behaved similarly with respect to patency in the long stent matrix (44.4% and 48.%, respectively). This subgroup analysis was not statistically powered. Diabetic Patients: There was a slight trend towards higher patency in the non-diabetic population for shorter lesions (<50 mm) and no differences seen in the MAE rate, but the findings were not statistically significant as the analysis was not sufficiently powered. Rutherford Classification: The subgroup analysis based on Rutherford classification (claudication vs. critical limb ischemia [CLI]) was not conclusive given the very small proportion of subjects with CLI (n=4). This analysis was not statistically powered. Stent Matrix: The last subgroup analysis was based on stent matrix (core vs. long vs. entire matrix) and was not statistically powered either. The findings showed very similar patency rates between the entire matrix and the core matrix, both showing an advantage over the long matrix as it should be expected. HOW SUPPLIED The Innova Vascular Self-Expanding Stent System is supplied sterile inside a pouch. The device is sterilized via Ethylene Oxide. The device is non-pyrogenic. Handling and Storage Do not use if package is opened or damaged. Do not use if labeling is incomplete or illegible. The packaged device should be stored in a cool, dark place, and temperatures should not exceed 5 C (4 F). RECOMMENDED MATERIALS in (0.89 mm) stiff guidewire of appropriate length (300 cm length recommended for 30 cm length stent delivery systems) Introducer or guide sheath of appropriate size and length and equipped hemostatic valve Luer lock syringe 0 ml (0 cc) for flushing the stent delivery system OPERATIONAL INSTRUCTIONS Patient Preparation The percutaneous placement of a self-expanding stent in a stenotic or obstructed artery should be done in an angiography procedure room with the appropriate imaging equipment. Patient preparation and sterile precautions should be the same as for any angioplasty procedure. Appropriate antiplatelet and anticoagulation therapy must be administered pre- and post-procedure in accordance with standard practices. Angiography should be performed to map out the extent of the lesion(s) and the collateral flow. Access vessels must be sufficiently patent to proceed with further intervention. If thrombus is present or suspected, thrombolysis should precede stent deployment using standard acceptable practice. 6 Inject Contrast Media Perform angiogram using standard technique. Evaluate and Mark the Stenosis Observe fluoroscopically the most distal view of the stenotic or obstructed artery. Obtain a road map image of the lesion area if necessary. Select Proper Stent System. Measure the diameter of the reference vessel (proximal and distal to the lesion or obstruction). Select a stent based on the table below to ensure a secure placement. Table summarizes the total intended Innova Vascular Self-Expanding Stent sizes. Table : Innova Vascular Self-Expanding Stent System Models and Sizes Stent Nominal Diameter (mm) Unconstrained Length (mm) Reference Vessel Diameter (mm) *All sizes may not be available in all regions. The Innova stent deployed length change from the delivery system is less than mm on average for stent lengths </= 40 mm and approximately 4.0% on average or less for all other stent lengths Measure the entire length of the actual lesion and select the proper length of the stent(s) to be deployed. To help ensure adequate apposition, it is recommended that the length of the stent be chosen so that the ends of the stent extend at least 5 mm beyond both ends of the lesion into healthy tissue. Should more than one stent be required to cover the lesion, allow for at least 5 mm of stent overlap. It is generally recommended that the distal stent be placed first. When multiple stents are required, if placement results in metal to metal contact, stent materials should be of similar composition. 3. Estimate the distance between the lesion and the entry site to select the proper stent delivery system length. Boston Scientific (Master Brand DFU Template 8.677in x.699in A4, 9000AA), edfu, MB, Innova Vascular, en, B

7 Preparation of Stent Delivery System. Open the outer box to reveal the pouch containing the stent delivery system.. Check the temperature exposure indicator on the pouch label to confirm that the product has not been compromised. See Warnings section. 3. After careful inspection of the pouch looking for damage to the sterile barrier, carefully peel open the pouch and extract the stent delivery system tray. 4. Carefully withdraw the stent delivery system from the tray by grasping the handle of the delivery system. 5. Examine the stent delivery system for any damage. If it is suspected that the sterility or integrity of the device has been compromised (i.e. kinking or missing component), the device should not be used. The device should not be used if the device is kinked, or if the thumbwheel lock is not attached. 6. Do not remove the thumbwheel lock prior to deployment. Premature removal of the thumbwheel lock may result in an unintended deployment of the stent. 7. Attach a 0 ml (0 cc) syringe filled with saline to the flushing luer 6 on the handle. Apply positive pressure. Continue to flush until saline appears at the distal end of the guidewire lumen. Remove the flushing luer 6 (by pulling the syringe or by pulling flushing luer 6) (Reference Figure 3). Thumbwheel Lock Thumbwheel 4 Pull Grip 3 6 Flushing Luer Radiopaque Tip Middle Shaft Radiopaque Marker Band 5 Radiopaque Distal Markers on Stent Radiopaque Proximal Markers on Stent (Approx. 3 mm) (Approx. 8mm) Figure 3. Delivery Procedures. Gain arterial access utilizing a 6F (. mm) or larger sheath with a hemostatic valve. Precautions: Always use an introducer or guide sheath for the implant procedure, to protect the access site and prevent system damage. Do not use a kinked delivery system. Kinking of the introducer/guide sheath at the access site can restrict the movement of the delivery system during deployment.. Pass an in (0.89 mm) guidewire of appropriate length (300 cm length recommended for 30 cm stent delivery systems) across the target lesion or obstruction. Notes: A stiff in guidewire is strongly recommended for deployment of the stent, especially for tortuous anatomy and contralateral approaches. Use of undersized guidewires may lead to insufficient support of the device which can compromise stent delivery. If using a hydrophilic guidewire, ensure that it is hydrated at all times. 3. Pre-dilate the lesion with a balloon dilatation catheter using conventional technique. After the lesion has been properly dilated, remove the dilatation catheter, leaving the guidewire with the tip distal to the lesion for stent system advancement. 4. Place the Innova Vascular Stent Delivery System over the guidewire. Advance the delivery system as a unit through the hemostatic valve of the introducer or guide sheath. Notes: Do not tighten toughy-borst such that it restricts the movement of the delivery system. Do not remove the thumbwheel lock prior to deployment. Premature removal of the thumbwheel lock may result in an unintended deployment of the stent. Stent Deployment Procedure (Reference Figure 3). Remove slack from the system by advancing the system just beyond the target lesion, then, pulling the system back until stent radiopaque markers are centered over the target lesion. Note: Prior to deployment, ensure adequate distance between the proximal end of the stent and the introducer/guide sheath to prevent deployment within the introducer/guide sheath.. Remove the thumbwheel lock by compressing the tabs and pulling. Confirm that the radiopaque markers are still properly positioned across the target lesion. 7 Precaution: If strong resistance is met with the introduction of the delivery system or if unable to initiate release of the stent, remove the entire system from the patient and introduce a new system. Notes: For optimal performance, keep the entire length of the delivery system that is outside the body as straight and stable as possible. To do so, remove slack from the system, maintain slight backward tension on the delivery system, and anchor the handle on the patient or operating table during deployment. Alternatively, the operator may straighten and stabilize the distal end of the blue outer shaft during deployment. Failure to eliminate slack (Reference Figure 4) and/or curvature of the delivery system catheter between the introducer/guide sheath and the delivery system handle during deployment may adversely affect deployment accuracy, especially in ipsilateral cases. If repositioning of the stent delivery system is required, reinserting the thumbwheel lock will prevent inadvertent deployment. Figure 4. Recommended Method of Deployment. While using fluoroscopy maintain position of the distal and proximal stent radiopaque markers relative to the targeted site. Roll the thumbwheel 4 of the deployment handle in the direction of the arrow indicated on the handle. Continue to roll thumbwheel until the middle shaft radiopaque marker band 5 passes the distal stent radiopaque markers. Watch for the distal stent radiopaque markers to begin separating: separation of the distal stent radiopaque markers signals that the stent is deploying. Boston Scientific (Master Brand DFU Template 8.677in x.699in A4, 9000AA), edfu, MB, Innova Vascular, en, B

8 . Continue to roll thumbwheel until the middle shaft radiopaque marker band 5 passes the proximal radiopaque markers of the stent resulting in full deployment, or until the white activation arrow is visible on the pull grip extension rod (for 50 mm to 00 mm length stents), which indicates that pull grip activation is required to complete stent deployment (Reference Figure 5). Long stents (50 mm to 00 mm length) will not be fully deployed by the thumbwheel alone. Notes: When activating the pull grip, avoid rapid deployment. Do not restrict movement of the thumbwheel 4 otherwise deployment difficulties could be encountered. Do not attempt to pull a partially expanded stent back into introducer/guide sheath as dislodgement may occur. Do not push or pull the delivery system during deployment as this may compromise stent length. Long stents (50 mm to 00 mm length) require the pull grip to be retracted only after the white activation arrow is visible to complete deployment. Activation Arrow Figure Long stents (50 mm to 00 mm length) require pull grip deployment after the white activation arrow becomes visible on the pull grip extension rod. Grasp the manual pull grip 3 and gently pull away from the handle in the direction of the arrow. Slowly pull back until the middle shaft radiopaque marker band 5 passes the proximal radiopaque markers of the stent resulting in full deployment. 4. View the delivery system under fluoroscopy, ensuring that the middle shaft radiopaque marker band 5 has crossed the proximal stent markers. The delivery system can now be withdrawn. 5. Grasp the guidewire a short distance from handle and repeatedly retract the system over the wire until fully removed. Use caution when withdrawing the stent delivery system and always manipulate under fluoroscopy. If unusual resistance is felt, carefully readvance and rotate the delivery system in an attempt to center the delivery system within the vessel, then carefully attempt to repeat withdrawal. Note: Avoid bending the guidewire excessively near the handle when retracting device to aid removal and prevent guidewire kinking. 6. If incomplete expansion exists within the stent at any point along the lesion, balloon dilatation can be performed utilizing standard PTA technique. Precaution: Never pre-dilate the stent using a balloon that is larger in diameter than the nominal (labeled) diameter of the stent. 7. Withdraw guidewire and sheath from patient and establish hemostasis per conventional technique. Post Procedure Assess patient for hematoma and/or other signs of bleeding at the puncture site. REFERENCES The physician should consult recent literature on current medical practice on stent implantation. WARRANTY Boston Scientific Corporation (BSC) warrants that reasonable care has been used in the design and manufacture of this instrument. This warranty is in lieu of and excludes all other warranties not expressly set forth herein, whether express or implied by operation of law or otherwise, including, but not limited to, any implied warranties of merchantability or fitness for a particular purpose. Handling, storage, cleaning and sterilization of this instrument as well as other factors relating to the patient, diagnosis, treatment, surgical procedures and other matters beyond BSC s control directly affect the instrument and the results obtained from its use. BSC s obligation under this warranty is limited to the repair or replacement of this instrument and BSC shall not be liable for any incidental or consequential loss, damage or expense directly or indirectly arising from the use of this instrument. BSC neither assumes, nor authorizes any other person to assume for it, any other or additional liability or responsibility in connection with this instrument. BSC assumes no liability with respect to instruments reused, reprocessed or resterilized and makes no warranties, express or implied, including but not limited to merchantability or fitness for a particular purpose, with respect to such instruments. Magnetom Trio is a trademark of Siemens Aktiengesellschaft CORPORATION. Syngo is a trademark of Siemens Aktiengesellschaft CORPORATION. Intera is a trademark of KONINKLIJKE PHILIPS ELECTRONICS N.V. CORPORATION. 8 Boston Scientific (Master Brand DFU Template 8.677in x.699in A4, 9000AA), edfu, MB, Innova Vascular, en, B

9 EC REP Boston Scientific Limited Ballybrit Business Park Galway IRELAND EU Authorized Representative Australian AUS Sponsor Address Boston Scientific (Australia) Pty Ltd PO Box 33 BOTANY NSW 455 Australia Free Phone Free Fax Argentina ARG Local Contact Para obtener información de contacto de Boston Scientific Argentina SA, por favor, acceda al link Legal Manufacturer Boston Scientific Corporation 300 Boston Scientific Way Marlborough, MA 075 USA USA Customer Service Do not use if package is damaged. Recyclable Package 05 Boston Scientific Corporation or its affiliates. All rights reserved. Boston Scientific (Master Brand DFU Template 8.677in x.699in A4, 9000AA), edfu, MB, Innova Vascular, en, B